Method of detecting gene polymorphism

Abstract

A method for detecting a genetic polymorphism(s) in a gene encoding cytochrome P450 using as oligonucleotide probes and/or oligonucleotide primers at least one sequence selected from the group consisting of an at least 13 nucleotide sequence within any of the nucleotide sequences as shown in SEQ ID NOS: 1 through 215, said at least 13 nucleotide sequence containing the 21st nucleotide, or a sequence complementary to said at least 13 nucleotide sequence.

1 . A method for detecting a genetic polymorphism(s) in a gene encoding cytochrome P450 using as oligonucleotide probes and/or oligonucleotide primers at least one sequence selected from the group consisting of an at least 13 nucleotide sequence within any of the nucleotide sequences as shown in SEQ ID NOS: 1 through 215, said at least 13 nucleotide sequence containing the 21st nucleotide, or a sequence complementary to said at least 13 nucleotide sequence.  
     
     
         2 . The method according to  claim 1 , wherein the polymorphism is a single-nucleotide polymorphism, a polymorphism caused by deletion, substitution or insertion of a plurality of nucleotides, or a VNTR or microsatellite polymorphism.  
     
     
         3 . A method for evaluating a drug, comprising evaluating the efficacy and safety of the drug metabolized by cytochrome P450 from the detection results obtained by the method according to  claim 1  or  2 .  
     
     
         4 . A method for screening a drug, comprising selecting a drug to be used with reference to the evaluation obtained by the method according to  claim 3 .  
     
     
         5 . A method for screening a drug, comprising comparing information about a polymorphism(s) in a gene encoding cytochrome P450 and/or a sequence complementary thereto with information about a polymorphism(s) in a gene encoding cytochrome P450 and/or a sequence complementary thereto obtained from a subject; analyzing the efficacy and/or safety of drugs metabolized by cytochrome P450; and selecting a drug to be used from the analysis results obtained.  
     
     
         6 . The method according to any one of  claims 1  to  5 , wherein the cytochrome P450 is at least one selected from the group consisting of 2A6, 2A13, 2B6, 2E, 2S1, 5A1, 7A1 and 7B1.  
     
     
         7 . An oligonucleotide selected from the group consisting of the nucleotide sequences as shown in SEQ ID NOS: 1 through 215 and sequences complementary thereto.  
     
     
         8 . An oligonucleotide prepared so as to include a gene polymorphic site present in a gene encoding cytochrome P450 and/or a sequence complementary thereto based on the information about a polymorphism(s) in the gene and/or the complementary sequence thereto.  
     
     
         9 . The oligonucleotide according to  claim 8 , wherein the oligonucleotide is designed such that the nucleotide at the 5′-end, the 3′-end or the center of the oligonucleotide corresponds to the gene polymorphic site.  
     
     
         10 . The oligonucleotide according to  claim 9 , wherein the oligonucleotide containing a gene polymorphic site is composed of two fragments being linked to each other, one fragment being hybridizable to the gene encoding a cytochrome P450 or the sequence complementary thereto and the other fragment being not hybridizable thereto, and said polymorphic site is positioned at the 5′-end or the 3′-end of the hybridizable fragment.  
     
     
         11 . The oligonucleotide according to  claim 9  or  10 , wherein the oligonucleotide consists of an at least 13 nucleotide sequence within any of the nucleotide sequences as shown in SEQ ID NOS: 1 through 215, said at least 13 nucleotide sequence containing the 21st nucleotide, or a sequence complementary to said at least 13 nucleotide sequence.  
     
     
         12 . An oligonucleotide which is designed in a genomic DNA region containing a gene polymorphic site in any of the nucleotide sequences as shown in SEQ ID NOS: 1 through 215 so that it is located within 1000 bp of the polymorphic site toward the 5′-end and/or the 3′-end of the genomic DNA region, and which has a length of 13-60 nucleotides.  
     
     
         13 . A microarray wherein the oligonucleotide according to any one of  claims 7  to  12  is immobilized on a support.  
     
     
         14 . A genetic polymorphism detection kit comprising the oligonucleotide according to any one of  claims 7  to  12  and/or the microarray according to  claim 13.